Silpa Suthram1,2,3, Taylor Sittler2,3 and Trey Ideker1,2

Plasmodium falciparum is the pathogen responsible for over 90% of human deaths from malaria1. Therefore, it has been the focus of a considerable research initiative, involving the complete DNA sequencing of the genome2, large-scale expression analyses3, 4, and protein characterization of its life-cycle stages5. The Plasmodium genome sequence is relatively distant from those of most other eukaryotes, with more than 60% of the 5,334 encoded proteins lacking any notable sequence similarity to other organisms2. To systematically elucidate functional relationships among these proteins, a large two-hybrid study has recently mapped a network of 2,846 interactions involving 1,312 proteins within Plasmodium6. This network adds to a growing collection of available interaction maps for a number of different organisms, and raises questions about whether the divergence of Plasmodium at the sequence level is reflected in the configuration of its protein network. Here we examine the degree of conservation between the Plasmodium protein network and those of model organisms. Although we find 29 highly connected protein complexes specific to the network of the pathogen, we find very little conservation with complexes observed in other organisms (three in yeast, none in the others). Overall, the patterns of protein interaction in Plasmodium, like its genome sequence, set it apart from other species.